Questiomycin A

Questiomycin A is a phenoxazine and a chromophore that has been found in Streptomyces and has antibacterial and anticancer activities.1,2,3,4,5 It is active against M. scrofulaceum, M. marinum, and M. intracellulare (MICs = 2.8, 11.3, and 5.6 μg/ml, respectively) but not M. tuberculosis, M. smegmatis, M. kansasii, or M. fortuitum (MICs = >45 μg/ml).3 It is also inactive against E. coli, P. aeruginosa, S. tymphimurium, S. aureus, or L. monocytogenes. It is cytotoxic to a variety of cancer cells, including MCF-7, A549, MIA PaCa-2, and LoVo-1 cells (IC50s = 1.67, 5.48, 7.16, and 20.03 μM, respectively) as well as human umbilical vein endothelial cells (HUVECs) but not human embryonic lung fibroblast cells (HELs; IC50s = 16.06 and >50 μM, respectively).4 Questiomycin A reduces the increased intracellular pH in a variety of cancer cell lines, as well as in HUVECs and HELs. It prevents lung metastasis in a B16 mouse melanoma model of metastasis when administered at a dose of 0.5 mg/kg simultaneously with B16 cells or every three days.5 It is also a chromophore product of the reducing agent 2-aminophenol oxidation (as 2-amino-phenoxazine-3-one) and has been used as a readout in the study of catalytic oxidation of 2-aminophenol by various metal-containing complexes.6,2 It has an absorbance of 435 nm in methanol.2

References
1. Anzai, K., Isono, K., Okuma, K., et al. New antibiotics, questiomycins A and B. Rikagaku Kenkyusho Hokoku 36, 577-583 (1960).
2. Jana, N.C., Patra, M., Brand•o, P., et al. Synthesis, structure and diverse coordination chemistry of cobalt(III) complexes derived from a Schiff base ligand and their biomimetic catalytic oxidation of o-aminophenols. Polyhedron 164, 23-34 (2019).
3. Shimizu, S., Suzuki, M., Tomoda, A., et al. Phenoxazine compounds produced by the reactions with bovine hemoglobin show antimicrobial activity against non-tuberculosis mycobacteria. Tohoku J. Exp. Med. 203(1), 47-52 (2004).
4. Che, X.-F., Zheng, C.-L., Akiyama, S.-I., et al. 2-Aminophenoxazine-3-one and 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one cause cellular apoptosis by reducing higher intracellular pH in cancer cells. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 87(4), 199-213 (2011).
5. Hongo, T., Miyano-Kurosaki, N., Kurosaki, K., et al. 2-Aminophenoxazine-3-one prevents pulmonary metastasis of mouse B16 melanoma cells in mice. J. Pharmacol. Sci. 114(1), 63-68 (2010).
6. Mukherjee, C., WeyhermÜller, T., Bothe, E., et al. A tetracopper(II)-tetraradical cuboidal core and its reactivity as a functional model of phenoxazinone synthase. Inorg. Chem. 46(23), 9895-9905 (2007).